Recent years, there are growing cases of applying separation technologies by means of a large-scale chromatography to the preparation of raw materials or key intermediate compounds for pharmaceuticals. In particular, among such separation technologies, a simulated moving bed process of chromatography that enables a continuous production and a large-scale production is becoming more popular as a method for efficiently carrying out optical separation by large-scale chromatography.
For the production of chemical compounds including raw materials and key intermediates compounds for pharmaceuticals, strict production management is required on the basis of a GMP (Good Manufacturing Practice) regulations. The GMP regulations require a precise history of the production of each compound per lot. In order to comply with the GMP regulations, the compounds are produced by a batch process in usual cases because raw materials to be used per lot are precisely determined.
Therefore, when compounds for pharmaceutical use are produced by means of a simulated moving bed process, a strict history management of lots of raw materials on the basis of the GMP regulations is required for the production of such compounds. In this case, the raw materials are to be produced by a batch-type process.
As a system for supplying a plurality of sample liquids prepared by batch-type processes continually to a simulated moving bed, there may be mentioned a series system and a parallel system. The series system may comprise a dissolving vessel for preparing a sample liquid, a holding vessel for holding the prepared sample liquid and charging it and a simulated moving bed connected in series through pipes thereto so as to allow the supply of the sample liquids. On the other hand, the parallel system may comprise two dissolving vessels for preparing sample liquids so as to allow the first vessel to supply the sample liquid to the simulated moving bed and the second vessel allows the preparation of a new sample liquid to be supplied next. In this parallel system, while the sample liquid is being fed from the first vessel to the simulated moving bed, the new sample liquid is being prepared in the second dissolving vessel. In other words, the parallel system uses the two dissolving vessels alternately by shifting them one after the other.
The above systems, however, have the common drawbacks that it is difficult to continue supplying the sample liquid from the dissolving vessel until each of the dissolving vessels becomes empty of the sample liquid. If the sample liquid would be fed until it become empty of the sample liquid, there may be an increasing risk that gas phase penetrates into the simulated moving bed through the pipe immediately following the last supply of the sample liquid. If the gas phase would penetrate into the simulated moving bed, a balance in pressure within the simulated moving bed may be rendered so unstable that a stable separation operation of the simulated moving bed may also become difficult. Therefore, the penetration of the gas phase into the simulated moving bed has to be avoided thoroughly upon the operations of the simulated moving bed.
In the above prior art technologies, therefore, in order to prevent the gas phase from contamination into the simulated moving bed, the sample liquid to be prepared in the dissolving vessel is set to be in the smallest possible amount that causes no gas phase penetrating into the pipe and then into the simulated moving bed. Moreover, as the sample liquid would have reached the predetermined amount, the series system may be arranged in such a manner that the sample liquid is allowed to be transferred to the holding vessel, whereas the parallel system may be arranged in such a manner that the sample liquid may be fed continually to the simulated moving bed by shifting the dissolving vessels alternately.
These prior art processes still suffer from the drawbacks, however, that the management of lots for the preparation of raw materials is difficult because a next sample liquid is prepared in the dissolving tank where the previously prepared sample liquid is still left therein so that the previously prepared liquid is contaminated with the new liquid to be prepared next in the identical dissolving vessel.